Critically ill patients are routinely provided analgesia and sedation to prevent pain and anxiety during invasive procedures. There is currently no universally accepted sedative regimen for critically ill patients. Thus, patients often receive a variety of drugs during their stay in an intensive care unit, often receiving a variety of drugs concurrently. Moreover, over sedation may occur leading to longer time on mechanical ventilation, prolonged stay in the intensive care unit, and increased brain dysfunction (e.g., delirium and coma). For many years, sedation guidelines have supported the use of gamma-aminobutyric-acid (GABA)-receptor agonists, including propofol and benzodiazepines (e.g., midazolam) for targeted sedation of ICU patients. However, these agents are associated with adverse effects such as respiratory depression, hypotension, bradycardia, hyperlipidemia, lack of orientation, and potential abuse. Accordingly, there remains a need in the art for safe and effective methods of sedating a patient undergoing critical care treatment.
Gaboxadol (4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol) (THIP)), described in U.S. Pat. Nos. 4,278,676, 4,362,731, 4,353,910, and WO 2005/094820, is a selective GABAA receptor agonist with a preference for δ-subunit containing GABAA receptors. In the early 1980s gaboxadol was the subject of a series of pilot studies that tested its efficacy as an analgesic and anxiolytic, as well as a treatment for tardive dyskinesia, Huntington's disease, Alzheimer's disease, and spasticity. In the 1990s gaboxadol moved into late stage development for the treatment of insomnia but failed to show significant effects in sleep onset and sleep maintenance in a three-month efficacy study. Additionally, patients with a history of drug abuse who received gaboxadol experienced a steep increase in psychiatric adverse events. As a result of these negative results the development of gaboxadol was terminated. It has now been found that gaboxadol may provide a safe and effective alternative for the sedation of patients undergoing critical care treatment.